Genome sequences contain the information needed for the development and function of a given species. Exploring conservation of DNA sequence between species is a tool for identifying critical code that is likely to be important for functions shared between species. Genomic information is deployed by transcription and differential expression may well be important for phenotypic distinctions among closely related species. Comparative transcription has not been extensively explored. We are performing DNA microarray profiling and deep sequencing experiments to probe expression in several of the newly sequenced Drosophila species. These expression data provide the only biological evidence for most of the predicted genes in these species. Conserved gene expression is outstanding evidence of function. Therefore, these data will also be used to validate gene models in Drosophila melanogaster. Many of the genes that must function correctly to prevent disease in humans are also found in Drosophila. In many cases, a family of related genes in humans is represented by only a single ortholog in Drosophila. This streamlined genome and simple, rapid, sophisticated and inexpensive toolbox of techniques make Drosophila a very important model system.&#8232;&#8232;Organisms store excess energy in lipid droplets. We performed a genome-wide screen to identify genes that alter lipid storage or utilization by RNA interference in Drosophila tissue culture cells. We then determined that many of these genes also function in mammalian cells. These data indicate that Drosophila is a valuable system for exploring normal and abnormal lipid storage. The doublesex gene encodes two members of the conserved DMRT family of transcription factors, a male-specific (DSXM) and a female-specific (DSXF) isoform. We have determined that DSXM is expressed in all the somatic cells that are in contact with the male germline from gonad formation to terminal differentiation begins following meiosis. This pattern, along with the fact that DSX is non-cell-autonomously required for male germline survival or perhaps stem cell renewal, suggests that DSXM directly regulates genes required for soma/germline communication in the male niche. We are developing tools that will allow us to determine what genes are directly regulated by DSXM.